Neurogenesis is a vital process in the brains of animals and humans, whereby new nerve cells are continuously generated throughout the life span of the organism. The newly born cells are able to differentiate into functional cells of the central nervous system and integrate into existing neural circuits in the brain. Neurogenesis is known to persist throughout adulthood in two regions of the mammalian brain: the subventricular zone (SVZ) of the lateral ventricles and the dentate gyrus of the hippocampus. In these regions, multipotent neural progenitor cells (NPCs) continue to divide and give rise to new functional neurons and glial cells (for review Gage Mol Psychiatry. 2000 May;5(3):262-9). It has been shown that a variety of factors can stimulate adult hippocampal neurogenesis, e.g., adrenalectomy, voluntary exercise, enriched environment, hippocampus dependent learning and anti-depressants (Yehuda. J Neurochem. 1989 Jul.;53(1):241-8, van Praag. Proc Natl Acad Sci U S A. 1999 Nov. 9;96(23):13427-31, Brown. J Eur J Neurosci. 2003
May; 17(10):2042-6, Gould. Science. 1999 Oct. 15; 286(5439):548-52, Malberg. J Neurosi. 2000 Dec. 15; 20(24):9104-10, Santarelli. Science. 2003 Aug. 8; 301(5634):805-9). Other factors, such as adrenal hormones, stress, age and drugs of abuse negatively influence neurogenesis (Cameron. Neuroscience. 1994 July; 61(2):203-9, McEwen. Neuropsychopharmacology. 1999 Oct.; 21(4):474-84, Kuhn. J. Neurosci. 1996 Mar. 15; 16(6):2027-33, Eisch. Am J Psychiatry. 2004 March; 161(3):426).
U.S. Pat. No. 5,397,785 describes a number of 4-acylaminopyridine derivatives and compositions as well as their use in the treatment of senile dementia and Alzheimer's Disease. U.S. Pat. No. 6,884,805 describes polymorph crystals of a 4-acylaminopyridine derivative and their use in activating a malfunctioned cholinergic neuron that is associated with memory loss disturbances.
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